Molecular Stem Cell Biology Laboratory

The laboratory has four main research branches: 

1. Lentiviral Gene therapy: we develop innovative lentiviral gene therapy strategies for metabolic disorders with a focus on lysosomal storage disorders. This consists of engineering ex vivo bone marrow stem cells with lentiviral vectors to reintroduce a therapeutic gene. We have modified this strategy to tackle difficult-to-reach tissues, such as the brain and muscles. This has resulted in successful pre-clinical developments for Pompe disease and Hunter disease, while new efforts are being made for CLN2 and CLN3. Importantly, we have established LentiCure, a non-profit company that aims at commercial development of gene therapies for reasonable and transparent pricing. 
2. Muscle-on-chip: Skeletal muscle is the largest organ and a crucial metabolic hub of the body. Traditional cell culture methods fail to reproduce the complex three-dimensional architecture of muscle and its function of enabling movement through contraction. Our lab developed a pipeline to generate human contractile 3D Tissue Engineered Skeletal Muscles (3D-TESMs) in vitro, using myogenic progenitor cells derived from hiPSCs. Using rapid prototyping, bio/micro-fabrication, and tissue-engineering we validated muscle-on-chip platforms to model skeletal muscle functionality and disease. The 3D-TESMs are currently used to study neuromuscular and metabolic diseases such as Pompe disease and as a platform to screen therapeutic strategies.
3. RNA therapeutics: Antisense oligonucleotides (ASOs) enable precise modulation of gene expression and RNA processing, offering therapeutic potential for genetic and metabolic diseases. We optimize ASO-based strategies targeting molecular defects in lysosomal and metabolic disorders. Advanced conjugation technologies and delivery enhancements such as the use of lipid nanoparticles are employed to improve potency, stability, and tissue penetration, particularly in challenging organs such as muscle tissue, which is our main focus. This approach has yielded promising preclinical results for Pompe disease, with ongoing efforts focused on expanding the pipeline, refining splicing modulation and upregulation strategies, and translating candidates toward clinical application.
4. Muscle stem cells and regeneration: Skeletal muscle is a highly regenerative tissue capable of repairing after damage. This potential is dependent on muscle stem cells, called satellite cells. Satellite cells are quiescent and become activated upon damage. Our lab has shown that the regenerative capacity of skeletal muscle is affected in Pompe disease, in line with observations in other neuromuscular disorders. Our goal is to understand why muscle regeneration becomes defective as disease progresses and to use this knowledge to develop clinical approaches that counteract this. These approaches include stimulating endogenous muscle repair and implementing stem cell replacement strategies.
5. Genetics. We maintain the Pompe disease GAA variant database, which is one of the few mutation databases available for a genetic disease in which, in a highly curated way, DNA variants are linked to clinical phenotypes. In addition, we are searching for genetic modifiers that can alter the natural course of Pompe disease and/or affect the response to therapy. We also provide extended diagnosis in cases where a pathogenic mutation cannot be found by the regular diagnostic pipeline. Such variants may include for example intronic splice variants, variants in the promoter, small deletions, uniparental isodisomies or mosaicisms. 
6. Clinical research. Our group is embedded within the Center of Lysosomal and Metabolic Diseases of the Erasmus MC, ensuring a strong link with the clinic. We study efficacy and safety of enzyme replacement therapy and genotype/phenotype relationships. This includes studies to assess pharmacokinetics, antibody formation, immunomodulation, and tissue pathology. 

See also http://scholar.google.nl/citations?user=uqArP9wAAAAJ&hl=nl&oi=ao

best publications throughout career:

Qiushi Liang#, Fabio Catalano#, Eva C Vlaar#, Joon M Pijnenburg, Merel Stok, Yvette van Helsdingen, Arnold G Vulto, Ans T van der Ploeg, Niek P van Til*, WWM Pim Pijnappel*.  (2022). IGF2-tagging of GAA Promotes Full Correction of Murine Pompe Disease at a Clinically Relevant Dosage of Lentiviral Gene Therapy. Mol Ther Methods Clin Dev. 2022 Sep 24;27:109-130. doi: 10.1016/j.omtm.2022.09.010. eCollection 2022 Dec 8. *shared last authorships.  IF 5.8 (Q2)

Development of gene therapy for classic infantile Pompe disease.

Alessandro Iuliano#; Erik van der Wal#, Claudine W. B. Ruijmbeek, Stijn L. M. in ’t Groen, W. W. M. Pim Pijnappel*, Jessica C. de Greef* andVittorioSaggiomo*. Coupling 3D Printing and Novel Replica Molding for In-House Fabrication of Skeletal Muscle Tissue Engineering Devices. Adv Mater Technol, 2020 vol 5, issue 9, 2000344. https://doi.org/10.1002/admt.202000344 *shared last authorships.  IF 8.8 (Q1).Editor's pick and featured in the 'Best of Advanced Materials Technologies 2020' virtual issue.

Development of muscle on a chip technology: advanced disease modeling in 3D using human iPSCs.

Bergsma AJ, In 't Groen SLM, van den Dorpel JJA, van den Hout HJMP, van der Beek NAME, Schoser B, Toscano A, Musumeci O, Bembi B, Dardis A, Morrone A, Tummolo A, Pasquini E, van der Ploeg AT, Pijnappel WWMP. A genetic modifier of symptom onset in Pompe disease. EBioMedicine. 2019 Mar 25. pii: S2352-3964(19)30193-8.  Highlighted in Editorial: Silent but significant - A synonymous SNV alters prognosis in Pompe disease.Lukas J, Hermann A, Giese AK.EBioMedicine. 2019 May;43:20-21. doi: 10.1016/j.ebiom.2019.04.015. Epub 2019 Apr 12. No abstract available.PMID: 30982766.IF 11.2 (Q1).

Identification of a genetic modifier for late onset Pompe disease. 

Niño MY#, In 't Groen SLM#, Bergsma AJ, van der Beek NAME, Kroos M, Hoogeveen-Westerveld M, van der Ploeg AT, Pijnappel WWMP. Extension of the Pompe mutation database by linking disease-associated variants to clinical severity. Hum Mutat. 2019 Nov; 40 (11): 1954-1967. doi: 10.1002/humu.23854. IF 4.7 (Q2).Top downloaded paper 2018-2019 and featured on the cover. 

Internationally used open source database for mutations causing Pompe disease along with clinical phenotypes.

Schaaf GJ, van Gestel TJM, In 't Groen SLM, de Jong B, Boomaars B, Tarallo A, Cardone M, Parenti G, van der Ploeg AT, Pijnappel WWMP. Satellite cells maintain regenerative capacity but fail to repair disease-associated muscle damage in mice with Pompe disease. Acta Neuropathol Commun. 2018 Nov 7;6(1):119. doi: 10.1186/s40478-018-0620-3. Highlighted in Editorial: Skeletal myopathy in Pompe disease: a failure of satellite cell activation?Hiniker A, Margeta M.Acta Neuropathol Commun. 2018 Nov 30;6(1):133. doi: 10.1186/s40478-018-0638-6. No abstract available.PMID: 30501636.IF 7.5 (Q1). 

Muscle stem cells as target for muscle-regenerative therapy in Pompe disease. 

van der Wal E, Herrero-Hernandez P, Wan R, Broeders M, in ’t Groen SLM, van Gestel TJM, van Ijcken WFJ, Cheung TH , van der Ploeg AT, Schaaf GJ, Pijnappel WW. Large-scale expansion of human iPSC-derived skeletal muscle cells for disease modeling and cell-based therapeutic strategies. Stem Cell Reports 2018 Jun 5;10(6):1975-1990. IF 7.2 (Q2).

Development of a protocol to generate high quality muscle stem cells from human iPSCs. 

van der Wal E#, Bergsma AJ#, Pijnenburg JM, van der Ploeg AT, Pijnappel WWMP. Antisense Oligonucleotides Promote Exon Inclusion and Correct the Common c.-32-13T>G GAA Splicing Variant in Pompe Disease. Mol Ther Nucleic Acids 7: 90-100 (2017). IF 10.1 (Q1).

Development of RNA-based therapy for late onset Pompe disease. 

Pijnappel WW*, Esch D*, Baltissen MP, Wu G, Mischerikow N, Bergsma AJ, van der Wal E, Han DW, Bruch Hv, Moritz S, Lijnzaad P, Altelaar AF, Sameith K, Zaehres H, Heck AJ, Holstege FC, Schöler HR, Timmers HT. A central role for TFIID in the pluripotent transcription circuitry. Nature. 2013 Mar 28;495(7442):516-9. *shared first authorships. IF 69.5 (number 1).

Mechanistic insight in the role of basal transcription in cellular reprogramming and differentiation from and into pluripotent stem cells. 

Pijnappel, W.W*, Schaft*, D, Roguev, A., Shevchenko, A., Tekotte, H., Wilm, M., Rigaut, G., Seraphin, B., Aasland, R., and Stewart, A.F. The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program. Genes Dev. 2001 15, 2991-3004. *shared first authorships.IF 12.8 (top 10%).

Identification of protein complexes involved in epigenetic regulation of gene expression in yeast. 

Pijnappel, W.W., Hendriks, H.F.J., Folkers, G.E., van den Brink, C.E., Dekker, E.J., Edelenbosch, C., van der Saag, P.T. & Durston, A.J. The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification. Nature 1993 366, 340-344. IF 69.5 (number 1).

Identification of a novel retinoid ligand involved in early pattern formation during Xenopus laevis development. 

Other publications:

Faraguna MC, Lambregts DAM, Barzel I, Jacobs EH, Hoogeveen-Westerveld M, van der Beek NAME, Pijnappel PWWM, Gasperini S, Preijers T, van den Hout JMP, van der Ploeg AT.Can Alpha-Glucosidase Activity in Plasma or Leukocytes Serve as a Biomarker for Future Gene Therapy in Classic Infantile Pompe Disease? BioDrugs. 2025 Nov 24. doi: 10.1007/s40259-025-00757-7. Online ahead of print. PMID: 41284148

Catalano F, Stevic D, Zundo G, Huizer TF, Dammou Z, Vlaar EC, Katsavelis D, van den Bosch JC, van den Hout HJMP, Oussoren E, van der Ploeg AT, Ruijter GJG, Schaaf G, Pijnappel WWMP. Domain-substituted IGF2 tag modulates targeting of lentiviral gene therapy for Hunter syndrome. EMBO Mol Med. 2025 Nov;17(11):3197-3226. doi: 10.1038/s44321-025-00314-3. Epub 2025 Sep 29. PMID: 41023195

Laksono BM, Bergsma AJ, Iuliano A, Veldhoen DY, van Nieuwkoop S, Boter M, Leijten L, Bauer L, Oude Munnink BB, Pijnappel WP, van Riel D. Elucidatingtherole of human skeletalmuscles in thepathogenesis of enterovirus D68 infection. Life Sci Alliance. 2025 Sep 5;8(11):e202503372. doi: 10.26508/lsa.202503372. Print 2025 Nov. PMID: 40912913

Nadine A M E van der Beek, Maudy T M Theunissen, Johanna M P van den Hout, Wilhelmus W M Pijnappel, Benedikt Schoser, Pascal Laforêt, Giancarlo Parenti, Pieter A van Doorn, Ans T van der Ploeg. Clinical insights in enzyme replacement therapy for metabolic storage disorders: lessons from Pompe disease. Lancet Neurology2025;  24: 230-245. 

Eric Lukas Voorn, Alejandro Lucia, John Vissing, on behalf of the 281st ENMC workshopstudygroup: Helene Alexanderson, Linda van den Berg, Asunción Bustos, Elise Duchesne, Charlotte van Esch, Ingrid de Groot, Jean-Yves Hogrel, Meredith K James, Hans Knoop, Madelon Kroneman, Thomas Krag, Alejandro Lucia, Sander Oorschot, KristinØrstavik, Pim Pijnappel, Alfredo Santalla, NannaScharffPoulsen, Tanja Taivassalo, John Vissing, Nicole Voet, Eric Voorn. 281st ENMC International Workshop: 2nd ENMC workshop on exercise training in muscle diseases; towards consensus-based recommendations on exercise prescription and outcome measures. Hoofddorp, The Netherlands, 4-6 October 2024. Neuromuscular Disorders. doi.org/10.1016/j.nmd.2025.105318.

Franken M, van der Wal E, Zheng D, den Hamer B, van der Vliet PJ, Lemmers RJLF, van den Heuvel A, Dorn AL, Duivenvoorden CGA, In't Groen SLM, Freund C, Eussen B, Tawil R, van Engelen BGM, Pijnappel WWMP, van der Maarel SM, de Greef JC. Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.Brain. 2024 Nov 18:awae379. doi: 10.1093/brain/awae379.PMID: 39556762.

Schoser B, van der Beek NAME, Broomfield A, Brusse E, Diaz-Manera J, Hahn A, Hundsberger T, Kornblum C, Kruijshaar M, Laforet P, Mengel E, Mongini T, Orlikowski D, Parenti G, Pijnappel WWMP, Roberts M, Scherer T, Toscano A, Vissing J, van den Hout JMP, van Doorn PA, Wenninger S, van der Ploeg AT. Start, switch and stop (triple-S) criteria for enzyme replacement therapy of late-onset Pompe disease: European Pompe Consortium recommendation update 2024. Eur J Neurol. 2024 Jun 14:e16383. doi: 10.1111/ene.16383.

In 't Groen SLM, Franken M, Bock T, Krüger M, de Greef JC, Pijnappel WWMP. A knock down strategy for rapid, generic, and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal muscle. Skelet Muscle. 2024 Feb 22;14(1):3. doi: 10.1186/s13395-024-00335-5.

Liang Q, Vlaar EC, Pijnenburg JM, Rijkers E, Demmers JAA, Vulto AG, van der Ploeg AT, van Til NP, Pijnappel WWMP. Lentiviral gene therapy with IGF2-tagged GAA normalizes the skeletal muscle proteome in murine Pompe disease. J Proteomics. 2024 Jan 16;291:105037. doi: 10.1016/j.jprot.2023.105037. Epub 2023 Oct 30. *shared first authorships

Fabio Catalano, Eva C. Vlaar, Zina Dammou, Drosos Katsavelis, Tessa F. Huizer, Giacomo Zundo, Marianne Hoogeveen-Westerveld, Esmeralda Oussoren, Hannerieke J.P.M. van den Hout, Gerben Schaaf, Karin Pike-Overzet, Frank J.T. Staal, Ans T. van der Ploeg, W.W.M. Pim Pijnappel. Lentiviral gene therapy for Mucopolysaccharidosis II with tagged IDS prevents life threatening pathology in peripheral tissues but fails to correct cartilage. Human Gene Ther 2024 Feb 2. doi: 10.1089/hum.2023.177.

Catalano F, Vlaar EC, Katsavelis D, Dammou Z, Huizer TF, van den Bosch JC, Hoogeveen-Westerveld M, van den Hout HJMP, Oussoren E, Ruijter GJG, Schaaf G, Pike-Overzet K, Staal FJT, van der Ploeg AT, Pijnappel WWMP. Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II. Mol Ther Methods Clin Dev. 2023 Nov 2;31:101149. doi: 10.1016/j.omtm.2023.101149. eCollection 2023 Dec 14. IF 5.8 (Q2). 

Alessandro Iuliano, Matthias Haalstra, RamkumarRaghuraman, Kevin Bielawski, Anjali P. Bholasing, Erik van der Wal, Jessica C. de Greef, W. W. M. Pim Pijnappel. Real-time and Multichannel Measurement of Contractility of hiPSC-Derived 3D Skeletal Muscle using Fiber Optics-Based Sensing. Adv. Mater. Technol.2023, 8, 2300845. doi.org/10.1002/admt.202300845. IF 8.8 (Q1).Recognized as a top viewed article* in Advanced Materials Technologies

van der Wal E#, Iuliano A#, In 't Groen SLM, Bholasing AP, Priesmann D, Sharma P, den Hamer B, Saggiomo V, Krüger M, Pijnappel WWMP*, de Greef JC*. Highly contractile 3D tissue engineered skeletal muscles from human iPSCs reveal similarities with primary myoblast-derived tissues. Stem Cell Reports. 2023 Oct 10;18(10):1954-1971. doi: 10.1016/j.stemcr.2023.08.014. Epub2023 Sep 28. #shared first authorships, *shared last authorships.IF 7.2 (Q2).

M Broeders, JGJ van Rooij, E Oussoren, TJM van Gestel, CA Smith, SJ Kimber, RM Verdijk, MAEM Wagenmakers, JMP van den Hout, AT van der Ploeg, R Narcisi, WWMP Pijnappel. Generation of a disease model for cartilage pathology in MPS VI using patient-derived and isogenic gene-corrected hiPSCs. Front BioengBiotechnol. 2022 Dec 6;10:949063. doi: 10.3389/fbioe.2022.949063. eCollection 2022. 

Vincenza Gragnaniello, Pim W.W.M.Pijnappel, Alessandro P.Burlina, Stijn L.M.In 't Groen, Daniela Gueraldi, Chiara Cazzorla, Evelina Maines, Giulia Polo, Leonardo Salviati, Giovanni Di Salvo, Alberto  B.Burlina, Newborn screening for Pompe disease in Italy: Long-term results and future challenges Molecular Genetics and Metabolism Reports, Volume 33, December 2022, 100929

Rodrigo Canibano-Fraile, LaurikeHarlaar, Carlos A. dos Santos, Marianne Hoogeveen-Westerveld, Jeroen A. A. Demmers, Tim Snijders, Philip Lijnzaad, Robert M. Verdijk, Nadine A. M. E. van der Beek, Pieter A. van Doorn, Ans T. van der Ploeg, Esther Brusse. W. W. M. Pim Pijnappel*, Gerben J. Schaaf.* Lysosomal glycogen accumulation in Pompe disease results in disturbed cytoplasmic glycogen metabolism. J Inherit Metab Dis. 2023 Jan;46(1):101-115..*shared last authorships. IF 4.7 (Q2). 

Qiushi Liang#, Eva C Vlaar#, Fabio Catalano#, Joon M Pijnenburg, Merel Stok, Yvette van Helsdingen, Arnold G Vulto, Wendy WJ Unger, Ans T van der Ploeg, WWM Pim Pijnappel*, Niek P van Til* (2022). Lentiviral Gene Therapy Prevents Anti-Human Acid α-Glucosidase Antibody Formation in Murine Pompe Disease. Mol Ther Methods Clin Dev Volume 25, 9 June 2022, Pages 520-532. https://doi.org/10.1016/j.omtm.2022.04.016. *shared last authorships.  IF 5.8 (Q2)

Vollebregt AAM, Hoogeveen-Westerveld M, Ruijter GJ, van den Hout H, Oussoren E, van der Ploeg AT, Pijnappel WWMP Effect of anti-iduronidase sulfatase antibodies in patients with Mucopolysaccharidosis type II treated with enzyme replacement therapy. J Pediatr. 2022 May 11:S0022-3476(22)00414-0. doi: 10.1016/j.jpeds.2022.05.008. Online ahead of print. IF 6.3 (top 10%).

Lee NC, Chang KL, In 't Groen SLM, de Faria DOS, Huang HJ, Pijnappel WWM, Hwu WL, Chien YH. Outcome of later-onset Pompe disease identified through newborn screening. J Pediatr. 2022 May;244:139-147.e2. doi: 10.1016/j.jpeds.2021.12.072. IF 6.3 (top 10%). 

van Kooten HA, Ditters IAM, Hoogeveen-Westerveld M, Jacobs EH, van den Hout JMP, van Doorn PA, Pijnappel WWMP, van der Ploeg AT, van der Beek NAME Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease. Orphanet J Rare Dis. 2022 Feb 2;17(1):31. doi: 10.1186/s13023-022-02175-2 IF 4.3 (Q2)

Rodrigo Canibano-Fraile, Emma Boertjes, StelaBozhilova, W.W.M. Pim Pijnappel, and Gerben Schaaf. An in vitro assay to quantify satellite cell activation using isolated myofibers. STARProtoc. 2021 Apr 23;2(2):100482. doi: 10.1016/j.xpro.2021.100482. eCollection 2021 Jun 18 (new Cell press journal, no IF yet)

Herrero-Hernandez P, Bergsma AJ, Pijnappel WWMP. Generation of human iPSC-Derived Myotubes to Investigate RNA-Based Therapies In Vitro. Methods Mol Biol. 2022;2434:235-243. doi: 10.1007/978-1-0716-2010-6_Book chapter.

In ’t Groen SLM*, Broeders M*, Pijnappel WWMP. (2020) CRISPR/Cas9-mediated gene editing in human induced pluripotent stem cells. in CRISPR-Cas Methods: Volume II. Nature Springer. 2020 Volume 2, page 235-270. Book chapter. https://doi.org/10.1007/978-1-0716-1657-4_16. #shared first authorships

Niño MY, In't Groen SLM, de Faria DOS, Hoogeveen-Westerveld M, van den Hout HJMP, van der Ploeg AT, Bergsma AJ, Pijnappel WWMP. Broad variation in phenotypes for common GAA genotypes in Pompe disease. Hum Mutat. 2021 Nov;42(11):1461-1472. doi: 10.1002/humu.24272. IF 4.7 (Q2).

Arnold J.J. Reuser, Ans T. van der Ploeg, Priya S. Kishnani, W.W.M. Pim Pijnappel. Lysosomal Storage Disorders (Eds Atul Mehta, Bryan Winchester, Terence Eagleton] - Chapter 13: Pompe Disease. Wiley. inpress. Bookchapter.

Douglas O. S. de Faria, Stijn L. M. in ‘t Groen, Marianne Hoogeveen‐Westerveld, Monica Y. Niño, Ans T. van der Ploeg, Atze J. Bergsma, W. W.M. Pim Pijnappel. Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease‐associated variants, common sequence variants, and results from newborn screening. Hum Mutat. 2021 Feb;42(2):119-134. doi: 10.1002/humu.24148. Epub 2020 Dec 21. IF IF 4.7 (Q2).

Esmee Oussoren, Margreet A.E.M. Wagenmakers, Bianca Link, Jan C. van der Meijden, W.W.M. Pim Pijnappel, George J.G. Ruijter, Mirjam Langeveld, Ans T. van der Ploeg. Hip disease in Mucopolysaccharidoses and Mucolipidoses: a review of mechanisms, interventions and future perspectives. 2021 Bone. 2021 Feb;143:115729. doi: 10.1016/j.bone.2020.115729. Epub 2020 Oct 29. IF 4.6 (Q2).

Atze J. Bergsma, Stijn L.M. in ’t Groen, Fabio Catalano, Manjiro Yamanaka, Satoru Takahashi, Toshika Okumiya, Ans T. van der Ploeg, W.W.M. Pim Pijnappel. A generic assay for the identification of splicing variants that induce nonsense-mediated decay in Pompe disease. 2020  Eur J Hum Gen., 2021 Mar;29(3):422-433. doi: 10.1038/s41431-020-00751-3. IF 5.3 (Q1).

Monica Y. NiñoMartinez, Mark Wijgerde, Douglas OliveiraSoares de Faria, Marianne Hoogeveen-Westerveld, ooHooAtze J. Bergsma, Mike Broeders, Nadine A.M.E van der Beek, Hannerieke J.M. van den Hout, Ans T. van der Ploeg, Frans W. VerheijenandW.W.M. Pim Pijnappel. Enzymatic Diagnosis of Pompe Disease: lessons from 28 years of experience. 2020 Eur J Hum Genet. 2021 Mar;29(3):434-446. doi: 10.1038/s41431-020-00752-2. Epub 2020 Nov 8.IF 5.3 (Q1).

Sheng Zhua, Anna Hing Yee Lawa, Ruixia Denga, Ellen Ngar Yun Poon, Chun Wai Loa, Anna Ka Yee Kwong, Rui Liang. Kelvin Yuen Kwong Chan, fWai Lap Wong, Kian ChengTan-Ung, W.W.M. Pim Pijnappel, Godfrey Chi Fung Chan, Sophelia Hoi Shan Chan. Generation of genomic-integration-free human induced pluripotent stem cells and the derived cardiomyocytes of X-linked dilated cardiomyopathy from DMD gene mutation. Stem Cell Research, Volume 49, December 2020, 102040. IF 1.5 (Q4).

M Broeders, K Smits, B Goynuk, E Oussoren, HJMP van den Hout, A van der Ploeg & W.W.M. Pim Pijnappel. A generic assay to detect aberrant ARSB splicing and mRNA degradation for the molecular diagnosis of MPS VI (2020) Mol Ther Methods Clin Dev. 2020 Sep 16;19:174-185. doi: 10.1016/j.omtm.2020.09.004. eCollection 2020 Dec 11.IF 5.8 (Q2)

Martijn P.T. Ernst, Mike Broeders*, Pablo Herrero-Hernandez*, Esmee Oussoren, Ans T. van der Ploeg, & W.W.M. Pim Pijnappel. Ready for repair? Gene editing enters the clinic for the treatment of human disease. Mol Ther Methods Clin Dev. 2020 Jul 3;18:532-557. doi: 10.1016/j.omtm.2020.06.022. eCollection 2020 Sep 11. IF 5.8 (Q2)

Poelman E, van den Dorpel J, Hoogeveen-Westerveld M, van den Hout J, van der Giessen LJ, van der Beek N, Pijnappel W, van der Ploeg AT. Effects of higher and more frequent dosing of alglucosidase alfa and immunomodulation on long-term clinical outcome of classic infantile Pompe patients. J Inherit Metab Dis. 2020 Jun 7. doi: 10.1002/jimd.12268. IF 4.7 (Q2). 

Kuijper EC, Bergsma AJ, Pijnappel WWMP, Aartsma-Rus A. Opportunities and challenges for antisense oligonucleotide therapies. J Inherit Metab Dis. 2020 May 11. doi: 10.1002/jimd.12251. IF 4.7 (Q2). 

Stijn L.M. in 't Groen, Douglas O.S. de Faria, Alessandro Iuliano, Johanna M.P. van den Hout, Hannie Douben, Trijnie Dijkhuizen, David Cassiman, Peter Witters, Miguel-Angel Barba Romero, Annelies de Klein, Galhana M. Somers-Bolman, Jasper J. Saris, Lies H. Hoefsloot, Ans T. van der Ploeg, Atze J. Bergsma, W.W.M. Pim Pijnappel. Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis. Mol Ther Methods Clin Dev. 2020 Jan 13;17:337-348. doi: 10.1016/j.omtm.2019.12.016. eCollection 2020 Jun 12. IF 5.8 (Q2)

van Kooten HA, Harlaar L, van der Beek NAME, van Doorn PA, van der Ploeg AT, Brusse E; Erasmus MC Pompe expert committee: van der Pol Chair WL, Brusse E, Ditters IAM, Harlaar L, Hoogendijk-Boon MJ, Huidekoper HH, Kompanje EJO, Oskam A, Pijnappel WWM, Sibbles BJ, van den Dorpel JJA, van der Beek NAME, van der Hout JMP, van der Kuy H, van der Ploeg AT, van Doorn PA, van Kooten HA, Vulto AG, Wagenmakers MAEM. Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria. NeuromusculDisord. 2019 Nov 22. pii: S0960-8966(19)31205-2. IF 3.5 (Q2).

Broeders M, Herrero-Hernandez P, Ernst MPT, van der Ploeg AT, Pijnappel WWMP. Sharpening the Molecular Scissors: Advances in Gene-Editing Technology. iScience. 2019 Dec 19;23(1):100789. doi: 10.1016/j.isci.2019.100789. IF 6.1 (Q1). 

Kobolák J, Molnár K, Varga E, Bock I, Jezsó B, Téglási A, Zhou S, Lo Giudice M, Hoogeveen-Westerveld M, Pijnappel WP, Phanthong P, Varga N, Kitiyanant N, Freude K, Nakanishi H, László L, Hyttel P, Dinnyés A. Modelling the neuropathology of lysosomal storage disorders through disease-specific human induced pluripotent stem cells. Exp Cell Res. 2019 Jul 15;380(2):216-233. doi: 10.1016/j.yexcr.2019.04.021. Epub 2019 Apr 27. IF 4.1 (Q3).

Gerben J. Schaaf, Rodrigo Canibano-Fraile, Tom van Gestel, Ans T. van der Ploeg andWWM Pim Pijnappel. Restoring the regenerative balance in neuromuscular disorders: satellite cell activation as therapeutic target in Pompe disease. Ann Transl Med. 2019 Jul;7(13):280. doi: 10.21037/atm.2019.04.48. Review.PMID: 31392192. IF 3.6 (Q3). 

Poelman E, Hoogeveen-Westerveld M, van den Hout JMP, Bredius RGM, Lankester AC, Driessen GJA, Kamphuis SSM, Pijnappel WWM, van der Ploeg AT. Effects of immunomodulation in classic infantile Pompe patients with high antibody titers. Orphanet J Rare Dis. 2019 Mar 22;14(1):71. doi: 10.1186/s13023-019-1039-z. IF 4.3 (Q2)

Labrijn-Marks I, Somers-Bolman GM, In 't Groen SLM, Hoogeveen-Westerveld M, Kroos MA, Ala-Mello S, Amaral O, Miranda CS, Mavridou I, Michelakakis H, Naess K, Verheijen FW, Hoefsloot LH, Dijkhuizen T, Benjamins M, van den Hout HJM, van der Ploeg AT, Pijnappel WWMP, Saris JJ, Halley DJ. Segmental and total uniparental isodisomy (UPiD) as a disease mechanism in autosomal recessive lysosomal disorders: evidence from SNP arrays. Eur J Hum Genet. 2019 Feb 8. IF 5.3 (Q1).

Tarallo A, Carissimo A, Gatto F, Nusco E, Toscano A, Musumeci O, Coletta M, Karali M, Acampora E, Damiano C, Minopoli N, Fecarotta S, Della Casa R, Mongini T, Vercelli L, Santoro L, Ruggiero L, Deodato F, Taurisano R, Bembi B, Dardis A, Banfi S, Pijnappel WWP, van der Ploeg AT, Parenti G. microRNAs as biomarkers in Pompe disease. Genet Med. 2019 Mar;21(3):591-600. doi: 10.1038/s41436-018-0103-8. Epub 2018 Jul 12. IF 8.8 (top 10%).

Kuperus E, van der Meijden JC, In 't Groen SLM, Kroos MA, Hoogeveen-Westerveld M, Rizopoulos D, Martinez MYN, Kruijshaar ME, van Doorn PA, van der Beek NAME, van der Ploeg AT, Pijnappel WWMP. The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease. PLoS One. 2018 Dec 7;13(12):e0208854. doi: 10.1371/journal.pone.0208854. eCollection 2018. IF 3.7 (Q2).

Poelman E, Hoogeveen-Westerveld M, Kroos-de Haan MA, van den Hout JMP, Bronsema KJ, van de Merbel NC, van der Ploeg AT, Pijnappel WWMP. High Sustained Antibody Titers in Patients with Classic Infantile Pompe Disease Following Immunomodulation at Start of Enzyme Replacement Therapy. J Pediatr. 2018 Apr;195:236-243.e3. doi: 10.1016/j.jpeds.2017.11.046. Epub 2018 Feb 7. IF 6.3 (top 10%). 

Bergsma AJ, van der Wal E, Broeders M, van der Ploeg AT, Pim Pijnappel WWM Alternative Splicing in Genetic Diseases: Improved Diagnosis and Novel Treatment Options. Int Rev Cell Mol Biol.2018;335:85-141. doi: 10.1016/bs.ircmb.2017.07.008. Epub 2017 Sep 12. IF 6.4 (Q1).

van der Wal E, Bergsma AJ, van Gestel TJM In 't Groen SLM, Zaehres H, Araúzo-Bravo MJ, Schöler HR, van der Ploeg AT, Pijnappel WWMP. GAA Deficiency in Pompe Disease Is Alleviated by Exon Inclusion in iPSC-Derived Skeletal Muscle Cells. Mol Ther Nucleic Acids 7: 101-115 (2017). IF 10.1 (Q1). DOI: 10.1016/j.omtn.2017.03.002

Pijnappel WW, van Doorn PA, van der Ploeg AT. Commentary. Clin Chem. 2017 Jan;63(1):48. doi: 10.1373/clinchem.2016.265280. No abstract available. IF 12.1 (number 1).

van der Ploeg AT, Kruijshaar ME, Toscano A, Laforêt P, Angelini C, Lachmann RH, Pascual Pascual SI, Roberts M, Rösler K, Stulnig T, van Doorn PA, Van den Bergh PYK, Vissing J, Schoser B; Bembi B, Broomfield A, Boentert M, Desnuelle C, Findling O, Hahn A, Díaz-Manera J, Hundsberger T, Kornblum C, Labarthé F, Laforet P, Mengel KE, Mongini T, Muller-Felber W, Parenti G, Pijnappel WP, Preisler N, Sacconi S, Talim B, Tardieu M, van der Beek NAME, Wenninger S.. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience. Eur J Neurol. 2017 Jun;24(6):768-e31. doi: 10.1111/ene.13285. Epub 2017 May 6. IF 6.2 (Q1). 

de Vries JM, Kuperus E, Hoogeveen-Westerveld M, Kroos MA, Wens SC, Stok M, van der Beek NA, Kruijshaar ME, Rizopoulos D, van Doorn PA, van der Ploeg AT, Pijnappel WW. Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy. Genet Med. 2017 Jan; 19 (1):90-97. IF 8.8 (top 10%).

Vollebregt AAM, Hoogeveen-Westerveld M, Kroos MA, OussorenE, Plug I, Ruijter GJ, van der Ploeg AT, Pijnappel WWMP. Genotype-phenotype relationship in mucopolysaccharidosis II: predictive power of IDS variants for the neuronopathic phenotype. Dev Med Child Neurol. 2017 Oct;59(10):1063-1070. doi: 10.1111/dmcn.13467. Epub 2017 May 25. IF 4.8 (Q1).

Stephan C.A. Wens, Gerben J. Schaaf, Michelle Michels,Michelle E. Kruijshaar, Tom J.M. van Gestel, Stijn in 't Groen, Joon Pijnenburg, Dick H.W. Dekkers, Jeroen A.A. Demmers,Lex B. Verdijk, Esther Brusse, Ron H.N. van Schaik,Ans T. van der Ploeg, Pieter A. van Doorn andW.W.M. Pim Pijnappel. Elevated Plasma Cardiac Troponin T Levels due to Skeletal Muscle Damage in Pompe Disease. Circ Cardiovasc Genet. (2016) Feb; 9(1):6-13. doi: 10.1161/CIRCGENETICS.115.001322. IF: 4.5 (Q1). 

Bergsma, A.J. In ’t Groen, S.L.M., Verheijen F. W., van der Ploeg, A.T., and Pijnappel, W.W.M. From cryptic towards canonical splicing in Pompe disease: a pipeline for the development of antisense oligonucleotides. Mol Ther-NucleicAcids, 2016 Sep 13;5(9):e361. IF 10.1 (Q1).

Schoser B, Laforêt P, Kruijshaar ME, Toscano A, van Doorn PA, van der Ploeg AT; European Pompe Consortium (EPOC). Collaborators: Broomfield A, Desnuelle C, van Doorn PA, Hahn A, Kruijshaar ME, Lachmann R, Laforêt P, Mengel E, Mongini T, Müller-Felber W, Padberg G, Parenti G, Pascual IP, Pijnappel WW, van der Ploeg AT, Roberts M, Schoser B, Talim B, Toscano A, Treur W, Vissing J. 208th ENMC International Workshop: Formation of a European Network to develop a European data sharing model and treatment guidelines for Pompe disease Naarden, The Netherlands, 26-28 September 2014. NeuromusculDisord. 2015 Aug;25(8):674-8.IF 3.5 (Q2).

Bronsema KJ, Bischoff R, Pijnappel WW, van der Ploeg AT, van de Merbel NC. Absolute Quantification of the Total and Antidrug Antibody-Bound Concentrations of Recombinant Human α-Glucosidase in Human Plasma Using Protein G Extraction and LC-MS/MS. AnalChem. 2015 Apr 21;87(8):4394-401. IF 8.0 (top 10%).

Schaaf GJ, van Gestel TJ, Brusse E, Verdijk RM, de Coo IF, van Doorn PA, van der Ploeg AT, Pijnappel WW. Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease. Acta Neuropathol Commun. 2015 Oct 28;3:65. IF 7.5 (Q1).

Favejee MM, van den Berg LE, Kruijshaar ME, Wens SC, Praet SF, Pim Pijnappel WW, van Doorn PA, Bussmann JB, van der Ploeg AT. Exercise training in adults with Pompe disease: the effects on pain, fatigue, and functioning. Arch Phys Med Rehabil. 2015 May;96(5):817-22. IF 4.0 (Q1) 

Bergsma AJ, Kroos M, Hoogeveen-Westerveld M, Halley D, van der Ploeg AT, Pijnappel WW.Identification and characterization of aberrant GAA pre-mRNA splicing in pompe disease using a generic approach. Hum Mutat. 2015 Jan;36(1):57-68 IF 4.7 (Q2).

de Esch CE, Ghazvini M, Loos F, Schelling-Kazaryan N, Widagdo W, Munshi ST, van der Wal E, Douben H, Gunhanlar N, Kushner SA, Pijnappel WW, de Vrij FM, Geijsen N, Gribnau J, Willemsen R. Epigenetic characterization of the FMR1 promoter in induced pluripotent stem cells from human fibroblasts carrying an unmethylated full mutation. Stem Cell Reports. 2014 Oct 14;3(4):548-55.IF 7.2 (Q2).

Schaaf G, Sage F, Stok M, Brusse E, Pijnappel WWM, Reuser A and vd Ploeg AT. Ex-vivo Expansion of Muscle-Regenerative Cells for the Treatment of Muscle Disorders. J Stem Cell Res Ther 2012 S11:003. No IF.

Spedale G, Timmers HT, Pijnappel WW. ATAC-king the complexity of SAGA during evolution. Genes Dev. 2012 Mar 15;26(6):527-41. IF 12.8 (top 10%).

Spedale G, Meddens CA, Koster MJ, Ko CW, van Hooff SR, Holstege FC, Timmers HT, Pijnappel WW. Tight cooperation between Mot1p and NC2β in regulating genome-wide transcription, repression of transcription following heat shock induction and genetic interaction with SAGA. Nucleic Acids Res. 2012 Feb;40(3):996-1008. IF: 19.1 (top 5%).  Recommended in Faculty of 1000. 

Choukrallah MA, Kobi D, Martianov I, Pijnappel WW, Mischerikow N, Ye T, Heck AJ, Timmers HT, Davidson I. Interconversion between active and inactive TATA-binding protein transcription complexes in the mouse genome. Nucleic Acids Res. 2012 Feb;40(4):1446-59. IF: 19.1 (top 5%).  

Zhou Y, Adolfs Y, Pijnappel WW, Fuller SJ, Van der Schors RC, Li KW, Sugden PH, Smit AB, Hergovich A, Pasterkamp RJ. MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis. Mol Cell Biol. 2011 Sep;31(17):3603-15. IF 5.1 (Q2). 

Helbig AO, Rosati S, Pijnappel PW, van Breukelen B, Timmers MH, Mohammed S, Slijper M, Heck AJ. Perturbation of the yeast N-acetyltransferase NatB induces elevation of protein phosphorylation levels. BMC Genomics. 2010 11:685. IF: 4.5 (Q2). 

Bonnet J., Wang Y.H., Spedale G., Atkinson R.A., Romier C., Hamiche A., Pijnappel W.W., Timmers H.T., Tora L., Devys D., Kieffer B. The structural plasticity of SCA7 domains defines their differential nucleosome-binding properties. EMBO Rep. 2010 11(8): 612-618. IF 9.0 (Q1).

Hah N., Kolkman A., Ruhl D.D., Pijnappel W.W., Heck A.J., Timmers H.T., Kraus W.L. A role for BAF57 in cell cycle-dependent transcriptional regulation by the SWI/SNF chromatin remodeling complex. Cancer Res. 2010 70(11):4402-4411. IF 13.3 (top 10%). 

Spedale G., Mischerikow N., Heck A.J., Timmers H.T., Pijnappel W.W. Identification of Pep4p as the protease responsible for formation of the SAGA-related SLIK protein complex. J Biol Chem. 2010 285(30):22793-22799. IF 5.4 (Q2).

Pijnappel W.W.*, Kolkman A.*, Baltissen M.P., Heck A.J., Timmers H.T. Quantitative mass spectrometry of TATA binding protein-containing complexes and subunit phosphorylations during the cell cycle. Proteome Sci. 2009 7:46. *shared first authorships.IF 2.8 (Q3). 

Mischerikow, N., Spedale, G., Altelaar, A.F.M., Timmers, H.T., Pijnappel W.W. and Heck, A.J.R. In-depth profiling of post-translational modifications on the related transcription factor complexes TFIID and SAGA. J Proteome Res. 2009 8: 5020-5030. IF 5.3 (Q1).  

Lau, N.-C., Kolkman, A., van Schaik, F.M.A., Mulder, K.W., Pijnappel, W.W., Heck, A.J., and Timmers, H.T. Human CCR4-Not complexes contain variable deadenylase subunits. Biochem J. 2009 422(3): 443-453. IF 3.7 (Q3). 

Pijnappel, W.W., and Timmers, H.T. Dubbing SAGA unveils new epigenetic crosstalk. Mol Cell. 2008 29: 152-154. IF 19.3 (top 5%).

Mousson, F., Kolkman, A., Pijnappel, W.W.*, Timmers, H.T.*, and Heck, A.J.* Quantitative proteomics reveals regulation of dynamic components within TATA-binding protein transcription complexes. Moll Cell Proteomics 2008 7: 845-852. *shared last authorships.IF 7.3 (top 10%). 

Vermeulen, M., Mulder*, K.W., Denissov*, S., Pijnappel, W.W.*, van Schaik, F.M., Varier, R.A., Baltissen, M.P., Stunnenberg. H.G., Mann, M., Timmers, H.T. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 2007 131: 58-69. * shared 2nd authorships. IF 66.8 (top 2%)

Synowski, S.A., van den Heuvel R.H., Mohammed, S., Pijnappel, P.W., Heck, A.J. (2006). Probing genuine strong interactions and post-translational modifications in the heterogeneous yeast exosome protein complex. Mol Cell Proteomics 2006 5: 1581-1592. IF 7.3 (top 10%).

Testa, G., Zhang, Y., Vintersten K., Benes, V., Pijnappel, W.W., Chambers, I., Smith, A.J., Smith, A.G., and Stewart, A.F. Engineering the mouse genome with bacterial artificial chromosomes to create multipurpose alleles. Nat Biotechnol. 2003 21: 443-447. IF 68.1 (top 2%). 

Shevchenko, A., Schaft, D., Roguev, A., Pijnappel, W.W., Stewart, A.F., and Shevchenko, A. (2002). Deciphering protein complexes and protein interaction networks by Tandem Affinity Purification (TAP) and mass spectrometry: analytical perspective. Mol Cell Proteomics 2002 1: 204-212. IF 7.3 (top 10%). 

Roguev, A., Schaft. D., Shevchenko, A., Pijnappel, W.W., Wilm, M., Aasland, R., and Stewart, A.F. The S. cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 20, 7137-7148. IF 14.0 (top 10%)

Pijnappel, W.W., Folkers, G.E., De Jonge, W.J., Verdegem, P.J.E., De Laat, S.W., Lugtenburg, J., van der Saag, P.T. & Durston A.J. Metabolism to a response pathway specific retinoid ligand during axial pattern formation. Proc Natl Acad Sci USA. 1998 95, 15424-15429. IF: 10.7 (Q1).

Durston, A.J., van der Wees, J., Pijnappel, W.W, van der Saag, P.T. & Godsave, S.F. Retinoids and related signals in the early development of the vertebrate central nervous system. Curr Top Dev Biol. 1998 40, 111-175. IF 5.2 (Q1). 

Durston, A.J., van der Wees, J., Pijnappel, W.W.,Schilthuis, J. & Godsave, S.F. Retinoid signalling and axial patterning during early vertebrate embryogenesis. Cell Mol Life Sci.199753, 339-349. IF 9.2 (Q1). 

Van der Leede, B.M., van den Brink, C.E., Pijnappel, W.W., Sonneveld, E., van der Saag, P.T. & van der Burg, B. Autoinduction of retinoic acid metabolism to polar derivatives with decreased biological activity in retinoic acid-sensitive, but not in retinoic acid resistant human breast cancer cells. J Biol Chem. 1997 272, 17921-17928. IF 5.4 (Q2).

Pijnappel, W.W, Hendriks, H.F.J. & Durston, A.J. Retinoidsignallingduring embryogenesis. Eur J Clin Nutr. 1996 50, Suppl. 3, S29-S31. IF 4.8 (Q2). 

Durston, A.J., van der Wees, J., Godsave, S.F., Pijnappel, W.W. & Schilthuis, J.G. Retinoidsignalling in thevertebrate embryo. Neth J Zool. 1996 46, 68-90. No IF.

Durston, A.J., van der Wees, J., Pijnappel, W.W., Schilthuis, J. & Godsave, S.F. Retinoids in early embryonic development. In: Organization of the early vertebrate embryo; eds. Zagris, N., Duprat, A.M., and Durston, A.J.; New York etc., Plenum press; Proc. NATO Adv. Study Inst., Spetsai, Greece, Sept. 1994; NATO ASI Series, Series A: Life Sciences, 279, 249-261. Book chapter.

Pijnappel, W.W., Hendriks, H.F.J. & Durston, A.J. Retinoids in embryonic development. Voeding 1992 53, 179-182. No IF. 

Dekker, L.V., De Graan, P.N.E., Pijnappel, P., Oestreicher, A.B. & Gispen, W.H. Noradrenaline release from streptolysin-O-permeated rat cortical synaptosomes: effects of calcium, phorbol esters, protein kinase inhibitors, and antibodies to the neuron-specific protein kinase C substrate B-50 (GAP-43). J Neurochem. 1991 56, 1146-1153. IF 5.5 (Q2). 

Dr. W.W.M. Pim Pijnappel, Professor, Head Molecular Stem Cell Biology group
Dr. Gerben Schaaf, Assistant Professor
Dr. Atze Bergsma, Assistant Professor
Dr. Fabio Catalano, Post-doctoral researcher
Dr. Alessandro Iuliano, Post-doctoral researcher
Giacomo Zundo, MSc PhD student
Dejan Stevic, MSc, PhD student
Max Hennink, Msc, PhD student
Miro Weitzel, PhD student
Federico Silvestri, MSc, PhD student
Carlo Castiglione, MSc, PhD Student
Tess van der Loo, MSc, PhD student
Davey vander Horst, MSc PhD student (PI: Dr. George Ruijter, Clinical Genetics)
Tessa Huizer, BSc, technician
Anjali Bholasing, BSc, technician
WassimOuhammou, BSc, technician
Jiaxin Wu, MSc, technician